Evidence has been obtained that ADP-ribosylation may be involved in the regulation of two essential cellular functions, rRNA processing and cyclic AMP metabolism. Newly synthesized 28S rRNA is unstable and is quickly degraded in cultured normal rat kidney (NRK) cells treated with the pyridine derivative, picolinic acid, or the ADP-ribosylation inhibitor, 5-methylnicotinamide. Precursor rRNA synthesis and 18S rRNA accumulation are unaffected. The ability of prostaglandin E1 (PGE1) to elevate intracellular cyclic AMP is potentiated about 5-fold in cells treated with picolinic acid and 50-80% in cells treated with 5-methylnicotinamide. This increased hormonal response in picolinic acid treated cells may be a result of a decreased synthesis of a protein which normally functions to attenuate hormonal response since cycloheximide and actinonycin D prevent the return to normal of the PGE1 response after removal of the picolinic acid.